title: HIV-1 gp120 accelerates Fas-mediated activation-induced human lamina propria T cell apoptosis.
abstract: Intestinal mucosa represents an important portal of entry of HIV and a site of virus reservoir and active replication. Recently, in HIV patients, an early depletion of intestinal lamina propria T lymphocytes (LPT) has been described. HIV-1 gp120 has been demonstrated to promote apoptosis in noninfected isolated peripheral blood T cells, therefore we investigated whether gpl20 modulates apoptosis of normal human intestinal lamina propria T cells. Purified T cells were obtained by immunomagnetic negative selection from human lamina propria mononuclear cells isolated from surgical specimens by enzymatic procedure. Cells were incubated with or without recombinant gpl20 (10 microg/ml) and cultured either in the absence of any stimulus or in the presence of plate-bound anti-CD3 Ab (OKT3) or soluble anti-CD2 Ab (T11(2) + T11[3]). Apoptosis was assessed by flow cytometric analysis after propidium iodide staining. We demonstrated that preincubation of normal LPT cells with HIV-1 gpl20 accelerates the apoptosis observed during CD2-pathway stimulation of LPT cells. This process is mediated by Fas/Fas ligand interaction and related to an increased induction of Fas ligand mRNA by gpl20. Therefore HIV-1 gp120 could contribute to the depletion of noninfected LPT cells inducing a premature cell death.
authors.affiliation: Immunology Department, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Boirivant
authors.forename: M
authors.initials: M
authors.lastname: Viora
authors.forename: L
authors.initials: L
authors.lastname: Giordani
authors.forename: A L
authors.initials: AL
authors.lastname: Luzzati
authors.forename: A M
authors.initials: AM
authors.lastname: Pronio
authors.forename: C
authors.initials: C
authors.lastname: Montesani
authors.forename: O
authors.initials: O
authors.lastname: Pugliese
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D018801:CD2 Antigens / Q000502:physiology; D015704:CD4 Antigens / Q000494:pharmacology; D003106:Colon / Q000276:immunology; D053222:Fas Ligand Protein; D015699:HIV Envelope Protein gp120 / Q000276:immunology* / Q000494:pharmacology; D015497:HIV-1 / Q000737:chemistry*; D006801:Humans; D007422:Intestines / Q000166:cytology; D008024:Ligands; D008562:Membrane Glycoproteins / Q000494:pharmacology; D009092:Mucous Membrane / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction / Q000276:immunology / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013997:Time Factors; D019014:fas Receptor / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*
chemical_list: D018801:CD2 Antigens; D015704:CD4 Antigens; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D015699:HIV Envelope Protein gp120; D008024:Ligands; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D019014:fas Receptor